Transient relay function of midline thalamic nuclei during long-term memory consolidation in humans

Abstract

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.The standard model of systems consolidation (e.g., Alvarez and Squire 1994) describes an initial stage in which the hippocampus binds together distributed neocortical representations during retrieval of recent memories. These neocortical representations code event features that are located in sensory-specific and multimodal representational areas in posterior parts of the brain, which are engaged during initial encoding. With consolidation, interconnectivity between these representational areas stabilizes, allowing retrieval of remote memories to be hippocampally independent. Accumulating evidence from animal and human work has extended this view by showing evidence for medial prefrontal cortex (mPFC) involvement during remote memory retrieval (Bontempi et al. 1999;Takashima et al. 2006; TakeharaNishiuchi and McNaughton 2008). The mPFC appears interacting with posterior representational areas during retrieval of remote memories (Frankland and Bontempi 2005), potentially binding them together (Takashima et al. 2006;Wheeler et al. 2013).The systems-level processes underlying this transition from a hippocampally to a neocortically dependent memory are not well understood, though there seems evidence for a hippocampalmPFC interaction underlying this process (van Kesteren et al. 2010). However, rodent hippocampal-mPFC fibers are unidirectional and rather unevenly distributed over the hippocampus (Vertes et al. 2007;Hoover and Vertes 2012) and thus, an indirect interaction appears necessary if a bidirectional information flow between mPFC and hippocampus is required during systems consolidation. The rat's thalamic midline structures (nucleus reuniens/rhomboid nucleus) are reciprocally connected to both the mPFC and hippocampus as well as to posterior representational areas (Aggleton and Brown 1999;Van der Werf et al. 2002;Vertes et al. 2006Vertes et al. , 2007Hoover and Vertes 2012;Cassel et al. 2013;Wheeler et al. 2013) that seems also evident in nonhuman primates (Amaral and Cowan 1980;DeVito 1980;Aggleton et al. 1986Aggleton et al. , 2011Hsu and Price 2007). Indeed, the nucleus reuniens acts as a hippocampal-mPFC relay during memory encoding in mice determining specificity/generalization of memory attributes (Xu and Südhof 2013). The nucleus reuniens seems als...

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

“…Thus, the unidirectional connection from hippocampus to mPFC may be reciprocated via routes through the thalamus. Indeed, a recent rodent study showed that the mPFC controls the excitability of hippocampal neurons via midline thalamic nuclei during fear memory encoding (Xu and S€ udhof, 2013), and in humans, it has been shown that midline thalamic nuclei mediate between mPFC and hippocampus during high-confidence memory retrieval (Thielen, Takashima, Rutters, Tendolkar, & Fern andez, 2015). Previous imaging studies have already shown that successfully and confidentially remembered associations lead to increased activation in hippocampal and medial prefrontal cortices during encoding (Sperling et al, 2003;Chua, Rand-Giovannetti, Schacter, Albert, & Sperling, 2004;Chua, Schacter, Rand-Giovannetti, & Sperling, 2007).…”

The transcription factor Shox2 shapes thalamocortical neuron firing and synaptic properties

“…Previous clinical studies demonstrate that proper thalamic function is critical for memory formation and consolidation. In humans, damage to the thalamic nuclei, especially medial and anterior nuclei, causes severe memory deficits known as diencephalic amnesia [12][13][14][15][16][17] . While the neural circuitry of the effects of Shox2 expression on recognition memory are unclear, perhaps these effects occur via effects on TCN connections to retrosplenial cortex as suggested by the anatomical connectivity indicated in our study (Fig.…”

“…Dysfunction of these oscillations caused by aberrant activity in the thalamic circuit is thought to play a role in many neuropathological conditions, including epilepsy [2][3][4] , autism [5][6][7] , and schizophrenia [8][9][10][11] . Furthermore, damage to thalamic nuclei, especially medial and anterior nuclei, causes severe memory deficits known as diencephalic amnesia [12][13][14][15][16][17] .…”

Aerobic Activity in the Healthy Elderly Is Associated with Larger Plasticity in Memory Related Brain Structures and Lower Systemic Inflammation

“…The thalamus has been described as an important structure regarding mPFC-hippocampus “communication” during memory processes. Evidence from human imaging studies as well as animal data revealed that the mPFC-thalamus-hippocampus axis is strongly associated with memory encoding (Xu and Südhof, 2013) memory consolidation (Thielen et al, 2015) and memory retrieval (Aggleton and Brown, 1999; Davoodi et al, 2009, 2011; Aggleton et al, 2010; Loureiro et al, 2012). Here, we show for the first time, that engagement in aerobic physical activity is associated with increased activation and functional connectivity in the mPFC-thalamus-hippocampal axis when elderly learn new face-occupation associations.…”

“…Anatomically, the hippocampus is strongly connected to prefrontal regions as medial prefrontal cortex (mPFC; Preston and Eichenbaum, 2013) which, in turn, have reciprocal connections to several thalamic nuclei that are indirectly or directly reciprocally connected to the hippocampus in monkey (Aggleton et al, 2011). Moreover, a recent fMRI study revealed functional connectivity between hippocampus, mPFC and thalamus during episodic memory retrieval in young adults (Thielen et al, 2015). Therefore, we hypothesize that face association learning (encoding) is associated with the hippocampal-thalamus-mPFC axis and that engagement in aerobic physical activity has a positive effect on activation and functional connectivity within this memory network.…”